FIELD OF THE INVENTION
[0001] The invention relates to a pediatric formula, and particularly relates to enhancing
the tolerance of pediatric patients fed the formula. Pediatric patients include both
infants (children 12 months of age or less) and children (children more than 12 months
of age but less than 13 yrs of age), (Therefore, all infants are children, but not
all children will be infants.) More specifically, the invention is a pediatric formula
comprising xanthan gum that has been found effective in increasing tolerance in patients
fed such a formula. The invention is also a method of providing nutrition and a method
of improving tolerance comprising administering an effective amount of a pediatric
formula comprising xanthan gum.
BACKGROUND OF THE INVENTION
[0002] Pediatric formulas may be classified into three general types based on the type of
protein: intact protein-based, hydrolyzed protein-based, and free amino acid-based.
(Pediatric formulas encompass infant formulas and formulas intended for children one
year and older.) Commercial pediatric formulas may also contain, in addition to a
protein source, carbohydrates, lipids, vitamins and minerals. Free amino acids are
currently utilized as the pediatric source in pediatric formulas (EleCare™, Ross Products
Division of Abbott Laboratories) intended for children one year and older who have
one or more of the following: problems digesting and absorbing regular foods, severe
food allergies, gastrointestinal tract problems, or other conditions in which an elemental
diet is needed.
[0003] Many pediatric patients experience intolerance to certain formulas (formula intolerance).
The terms intolerance and formula intolerance are used interchangeably herein. Intolerance
is a non-immune system associated reaction and may be evidenced by behavior or stool
or feeding pattern changes such as increased spit-up or vomiting, an increased number
of stools, more watery stools, and increased fussiness as compared to normal infants
who tolerate formula well. Intolerance is most often indicated by gastrointestinal
symptoms (e.g. emesis, stool patterns and gas) as well as behavioral characteristics
(e.g. acceptance of formula, fussing and crying). In clinical study settings such
behavior may be cause for parents to remove their infants from a particular study.
Infants removed from a study because of such behaviors are referred to as exits for
intolerance. In a non-clinical setting such behavior often causes parents to switch
formulas.
[0004] Intolerance can be contrasted with the allergic-type reactions some infants exhibit
to certain formulas. These allergic-type reactions are immune system associated, and
may be caused by the infant's sensitivity to the protein present in the formula. Many
infants who exhibit allergies or sensitivities to intact (whole) proteins, such as
those in intact cow's milk protein or intact soy protein isolate-based formulas, are
able to tolerate extensively hydrolyzed protein. (Hydrolysate formulas (also referred
to as semi-elemental formulas) contain protein that has been hydrolyzed or broken
down into short peptide fragments and amino acids and as a result is more easily digested
by all infants.) These immune system associated allergies or sensitivities often result
in cutaneous, respiratory or gastrointestinal symptoms such as vomiting and diarrhea.
Infants who exhibit reactions to intact protein formulas often will not react to hydrolysate
formulas because their immune system does not recognize the hydrolyzed protein as
the intact protein that causes their symptoms. Infants who exhibit immune system associated
reactions to formulas may also exhibit non-immune system associated reactions (formula
intolerance), as previously described.
[0005] Many different pediatric formulas are in existence. Much of the previous focus in
the art has been on the physical stability of the formulas, and concurrent processing
or manufacturing concerns.
[0006] U.S. Patent 5,192,577 to Masson discloses and teaches the use of xanthan gum in a
nutritional formula but only as a stabilizer and specifically limits that use to formulas
that use kappa carrageenan in combination with the xanthan gum. Masson deals primarily
with the physical stability of the nutritional formula disclosed therein and does
not address the problem of intolerance exhibited by patients fed the formula.
[0007] U.S. Patent 5,472,952 to Smidt et al. relates to nutritionally complete food compositions
which contain partially hydrolyzed pectin for the management of diarrhea. The use
of xanthan gum as an emulsifier or stabilizer is disclosed but no teaching of the
amount of xanthan gum is provided.
[0008] U.S. Patent 5,681,600 to Antinone et al. discloses use of xanthan gum in a nutritional
formula but teaches that such use of xanthan gum is unacceptable because of unacceptable
calcium delivery resulting from use of formulas comprising xanthan gum.
[0009] U.S. Patent 4,670,268 to Mahmoud discloses an enteral nutritional hypoallergenic
nutritional formula which may contain xanthan gum as a stabilizer but fails to provide
any teaching of effective amounts of xanthan gum for that purpose.
[0010] U.S. Patent 5,919,512 to Montezinos discloses the use of xanthan gum as a stabilizer
in a flavor/cloud emulsion such as is present in dilute juice and tea beverages. The
emulsion disclosed therein contains no protein and thus, would be unsatisfactory for
use as a pediatric formula.
[0011] U.S. Patent 5,597,595 to DeWille et al. discloses the use of xanthan gum as an emulsion
stabilizer in a low pH beverage fortified with calcium and vitamin D.
[0012] U.S. Patent 5,817,351 to DeWille et al. discloses the use of xanthan gum as a stabilizer
in low pH beverages that are calcium fortified. The beverages disclosed therein contain
no fat and protein and would be unsuitable as a complete nutritional source.
[0013] U.S. Patent 5,609,897 to Chandler et al. discloses the use of xanthan gum in a soft
drink like powdered beverage that has been fortified with calcium and vitamin D.
[0014] U.S. Patent 5,858,449 to Crank et al. discloses the use of xanthan gum in an isoflavone-enriched
soy-based frozen dessert.
[0015] In general, the prior art nutritional formulas completely fail to address the problem
of intolerance. Thus, there is an unmet need for a formula that is more readily tolerated
by pediatric patients who exhibit symptoms of intolerance. A formula that is better
tolerated will result in behavior more similar to that displayed by normal pediatric
patients who tolerate formula well.
SUMMARY OF THE INVENTION
[0016] The present invention provides an improved pediatric formula and methods for providing
nutrition and increasing the tolerance of children fed the formula. (As used herein,
unless otherwise indicated, the term children is meant to encompass both infants and
children over one year in age. The terms child/children and pediatric patient are
also used interchangeably.) The use of xanthan gum has provided unexpected improvements
in tolerance. The formula may be in liquid concentrate, ready-to-feed or powdered
form. The formula comprises, based on a 100 kcal basis, about 8 to about 16 grams
carbohydrate (preferably about 9.4 to about 12.3 grams), about 3 to about 6 grams
lipid (preferably about 4.7 to about 5.6 grams), about 1.8 to about 3.3 grams protein
(preferably about 2.4 to about 3.3 grams), and a tolerance improver comprising about
37 to about 370 milligrams (preferably about 74 to about 222 milligrams, more preferably
about 111 to about 148 milligrams) xanthan gum. If the formula is provided in a powder
form, it comprises based on 100 grams of powder, about 30 to about 90 grams carbohydrate
(preferably about 48 to about 59 grams), about 15 to about 30 grams lipid (preferably
about 20 to about 30), about 8 to about 17 grams protein (preferably about 10 to about
17 grams), and about 188 to about 1880 milligrams (preferably about 375 to about 1125
milligrams, more preferably about 565 to about 750 milligrams) xanthan gum.
[0017] The formula may further comprise a stabilizer and also preferably comprises vitamins
and minerals in amounts sufficient to supply the daily nutritional requirements of
infants or children over one. When the formula is an infant formula, the amounts of
vitamins and minerals are preferably selected according to FDA guidelines. When infants
are fed a formula according to the invention, improved tolerance is exhibited by those
infants, as compared to infants fed a formula with the same composition but lacking
the tolerance improver.
[0018] The invention also provides methods of providing nutrition to and improving tolerance
in a pediatric patient. The methods comprise feeding the child an effective amount
of a formula comprising, based on a 100 kcal basis, about 8 to about 16 grams carbohydrate
(preferably about 9.4 to about 12.3 grams), about 3 to about 6 grams lipid (preferably
about 4.7 to about 5.6 grams), about 1.8 to about 3.3 grams protein (preferably about
2.4 to about 3.3 grams), and a tolerance improver comprising about 37 to about 370
milligrams (preferably about 74 to about 222 milligrams, more preferably about 111
to about 148 milligrams) xanthan gum. If the formula is provided in a powder form,
it comprises based on 100 grams of powder, about 30 to about 90 grams carbohydrate
(preferably about 48 to about 59 grams), about 15 to about 30 grams lipid (preferably
about 22 to about 28), about 8 to about 17 grams protein (preferably about 11 to about
17 grams), and about 188 to about 1880 milligrams (preferably about 375 to about 1125
milligrams, more preferably about 565 to about 750 milligrams) xanthan gum. Children
fed formulas of the invention exhibit fewer symptoms of intolerance than children
fed the same formula but lacking the xanthan gum tolerance improver.
DETAILED DESCRIPTION OF THE INVENTION
[0019] The present invention provides an improved pediatric formula that reduces the intolerance
of children fed the formula. The invention also provides methods for providing nutrition
to and improving tolerance in pediatric patients comprising feeding a formula of the
invention. The use of xanthan gum has provided unexpected improvements in tolerance.
[0020] Intolerance (formula intolerance) in infants is often indicated by gastrointestinal
symptoms (e.g. emesis, stool patterns, and gas) as well as behavioral characteristics
(e.g. acceptance of formula, fussing, and crying). For purposes of this invention,
improved tolerance (or reduced intolerance) is defined as an improvement (change towards
normal patterns) of one or more of the following symptoms or characteristics: stool
pattern, vomiting, spit up, acceptance of formula, fussing, crying, or exits for intolerance
(clinical setting).
[0021] The pediatric formula of the invention may be provided in powdered, liquid concentrate
or ready-to-feed forms. Before feeding, water is added to both the powdered and concentrate
forms of the formula. In a first embodiment, a pediatric formula of the invention
comprises, based on a 100 kcal basis, about 8 to about 16 grams carbohydrate (preferably
about 9.4 to about 12.3 grams), about 3 to about 6 grams lipid (preferably about 4.7
to about 5.6 grams), about 1.8 to about 3.3 grams protein (preferably about 2.4 to
about 3.3 grams), and a tolerance improver comprising about 37 to about 370 milligrams
(preferably about 74 to about 222 milligrams, more preferably about 111 to about 148
milligrams) xanthan gum. If provided in a powder form, the formula comprises, based
on 100 grams of powder, about 30 to about 90 grams carbohydrate (preferably about
48 to about 59 grams), about 15 to about 30 grams lipid (preferably about 22 to about
28), about 8 to about 17 grams protein (preferably about 11 to about 17 grams), and
about 188 to about 1880 milligrams (preferably about 375 to about 1125 milligrams,
more preferably about 565 to about 750 milligrams) xanthan gum. A summary of the carbohydrate,
lipid and protein ranges (on a per 100 kcal basis, per 100 grams powder basis and
per liter basis (as fed concentration) for a formula according to the invention is
provided in Table I.
[0022] Xanthan gum is a high molecular weight polysaccharide produced by fermentation of
a carbohydrate by
Xanthomonas carnpestris. While xanthan gum is available in various mesh sizes, the use of xanthan gum in this
invention is not limited to any particular mesh size. An appropriate mesh size may
be selected based on processing parameters,
e.g., a finer mesh size (200 mesh) may be preferred if the xanthan gum is to be dry blended
into a formula whereas, a more coarse size (80 mesh) may be preferred if the xanthan
gum is not dry blended into a formula. A suitable xanthan, gum for use in this invention
is Keltrol_ F Xanthan Gum (200 mesh) available from Kelco, a division of Monsanto,
Chicago, Illinois.
[0023] Suitable carbohydrates, lipids and proteins can vary widely and are well known to
those skilled in the art of making pediatric formulas. Suitable carbohydrates may
thus include, but are not limited to, hydrolyzed, intact, naturally and/or chemically
modified starches sourced from corn, tapioca, rice or potato in waxy or non waxy forms;
and sugars such as glucose, fructose, lactose, sucrose, maltose, high fructose corn
syrup, and mixtures thereof. Maltodextrins are polysaccharides obtained from the acid
or enzyme hydrolysis of starches such as those from corn or rice. Their classification
is based on the degree of hydrolysis and is reported as dextrose equivalent (DE).
When protein hydrolysates are the protein source, the DE of any maltodextrin utilized
is preferably less than about 18-20. When protein hydrolysates are the protein source
it is also preferable to avoid conditions which could lead to the formation of excessive
Maillard browning products.
[0024] Suitable lipids include, but are not limited to, coconut oil, soy oil, corn oil,
olive oil, safflower oil, high oleic safflower oil, MCT oil (medium chain triglycerides),
sunflower oil, high oleic sunflower oil, palm oil, palm olein, canola oil, lipid sources
of arachidonic acid and docosahexaneoic acid, and mixtures thereof. Lipid sources
of arachidonic acid and docosahexaneoic acid include, but are not limited to, marine
oil, egg yolk oil, and fungal oil.
[0025] Suitable protein sources include milk, soy, rice, meat (e.g., beef), animal and vegetable
(e.g., pea, potato), egg (egg albumen), gelatin, and fish. Suitable intact proteins
include, but are not limited to, soy based, milk based, casein protein, whey protein,
rice protein, beef collagen, pea protein, potato protein and mixtures thereof. Suitable
protein hydrolysates also include, but are not limited to, soy protein hydrolysate,
casein protein hydrolysate, whey protein hydrolysate, rice protein hydrolysate, potato
protein hydrolysate, fish protein hydrolysate, egg albumen hydrolysate, gelatin protein
hydrolysate, a combination of animal and vegetable protein hydrolysates, and mixtures
thereof. Hydrolyzed proteins (protein hydrolysates) are proteins that have been hydrolyzed
or broken down into shorter peptide fragments and amino acids. Such hydrolyzed peptide
fragments and free amino acids are more easily digested. In the broadest sense, a
protein has been hydrolyzed when one or more amide bonds have been broken. Breaking
of amide bonds may occur unintentionally or incidentally during manufacture, for example
due to heating or shear. For purposes of this invention, the term hydrolyzed protein
means a protein which has been processed or treated in a manner intended to break
amide bonds. Intentional hydrolysis may be effected, for example, by treating an intact
protein with enzymes or acids. The hydrolyzed proteins that are preferably utilized
in formulas according to this invention are hydrolyzed to such an extent that the
ratio of the amino nitrogen (AN) to total nitrogen (TN) ranges from about 0.1 AN to
1.0 TN to about 0.4 AN to about 1.0 TN, preferably about 0.25 AN to 1.0 TN to about
0.4 AN to about 1.0 TN. (AN:TN ratios given are for the hydrolysate protein source
alone, and do not represent the AN:TN ratio in the final pediatric nutritional formula
product, since free amino acids may be added as a supplement and would alter the reported
value.) Protein may also be provided in the form of free amino acids. A formula according
to the invention is preferably supplemented with various free amino acids in order
to provide a more nutritionally complete and balanced formula. Examples of suitable
free amino acids include, but are not limited to, tryptophan, tyrosine, cystine, taurine,
L-methionine, L-arginine, and camitine.
[0026] A formula of the invention preferably also contains vitamins and minerals in an amount
designed to supply the daily nutritional requirements of a pediatric patient. The
formula preferably includes, but is not limited to, the following vitamins and minerals:
calcium, phosphorus, sodium, chloride, magnesium, manganese, iron, copper, zinc, selenium,
iodine, and Vitamins A, E, C, D, K and the B complex. Further nutritional guidelines
for infant formulas can be found in the Infant Formula Act, 21 U.S.C. section 350(a).
The nutritional guidelines found in the Infant Formula Act continue to be refined
as further research concerning infant nutritional requirements is completed. This
invention is intended to encompass formulas containing vitamins and minerals that
may not currently be listed in the Act.
[0027] In a second embodiment of the invention, the invention formula further comprises
a stabilizer. Suitable stabilizers for use in pediatric nutritional formulas are well
known to those skilled in the art. Suitable stabilizers include, but are not limited
to, gum arabic, gum ghatti, gum karaya, gum tragacanth, agar, furcellaran, guar gum,
gellan gum, locust bean gum, pectin, low methoxyl pectin, gelatin, microcrystalline
cellulose, CMC (sodium carboxymethylcellulose), methylcellulose hydroxypropyl methyl
cellulose, hydroxypropyl cellulose, DATEM (diacetyl tartaric acid esters of mono-
and diglycerides), dextran, carrageenans, and mixtures therecf. A formula according
to the invention preferably is free of kappa carrageenan as a stabilizer, and most
preferably is free of a carrageenan. A formula is defined as being free of kappa carrageenan
if any carrageenan utilized is predominately in another form (iota or lambda). For
purposes of this invention, free of kappa carrageenan or free of carrageenan means
that no kappa carrageenan or carrageenan is added during manufacturing. The amount
of stabilizers utilized will vary depending upon the stabilizer(s) selected, the other
ingredients present, and the stability and viscosity of the formula that is sought.
Appropriate amounts can be determined by those of skill in the art based on the particular
characteristics
(e.g., viscosity) being sought in the formula.
[0028] The invention also provides methods of providing nutrition to and improving tolerance
in a pediatric patient. The methods comprise feeding the child an effective amount
of a formula comprising, based on a 100 kcal basis, about 8 to about 16 grams carbohydrate
(preferably about 9.4 to about 12.3 grams), about 3 to about 6 grams lipid (preferably
about 4.7 to about 5.6 grams), about 1.8 to about 3.3 grams protein (preferably about
2.4 to about 3.3 grams), and a tolerance improver comprising about 37 to about 370
milligrams (preferably about 74 to about 222 milligrams, more preferably about 111
to about 148 milligrams) xanthan gum. If the formula is provided in a powder form,
it comprises based on 100 grams of powder, about 30 to about 90 grams carbohydrate
(preferably about 48 to about 59 grams), about 15 to about 30 grams fat (preferably
about 22 to about 28), about 8 to about 17 grams protein (preferably about 11 to about
17 grams), and about 188 to about 1880 milligrams (preferably about 375 to about 1125
milligrams, more preferably about 565 to about 750 milligrams) xanthan gum.
[0029] In another embodiment, the formula may further comprise a stabilizer. Either embodiment
also preferably comprises vitamins and minerals, in amounts as discussed above. Suitable
carbohydrates, lipids, proteins or proteins, and stabilizers are well known to those
skilled in the art and may include, but are not limited to, the substances described
above. Preferably, if the formula is an infant formula, the method comprises feeding
a sufficient amount of the formula to fulfill all of the infant's daily nutritional
requirements.
[0030] The pediatric formulas of this invention can be manufactured using techniques well
known to those skilled in the art. Various processing techniques exist for producing
powdered, ready-to-feed and concentrate liquid formulas. Typically, these techniques
include formation of a slurry from one or more solutions which may contain water and
one or more of the following: carbohydrates, proteins, lipids, stabilizers, vitamins
and minerals. This slurry is emulsified, homogenized and cooled. Various other solutions
may be added to the slurry before processing, after processing or at both times. The
processed formula is then sterilized and may be diluted to be utilized on a ready-to-feed
basis or stored in a concentrated liquid or a powder. If the resulting formula is
meant to be a ready-to-feed liquid or concentrated liquid, an appropriate amount of
water would be added before sterilization. If the resulting formula is meant to be
a powder, the slurry will be heated and dried to obtain a powder. The powder resulting
from drying may be dry blended with further ingredients, if desired.
[0031] The following examples are illustrative of the methods and compositions of the invention
for improving tolerance in pediatric patients. While the invention is described in
terms of a powdered infant nutritional formula in the examples, below, it is not intended
to be so limited, as it is intended to encompass both ready-to-feed and concentrate
liquid infant formulas as well as formulas for children one year in age or older.
The examples are not intended to be limiting as other carbohydrates, lipids, proteins,
stabilizers, vitamins and minerals may be used without departing from the scope of
the invention.
Example 1 - Clinical Study
[0032] Following is a summary of the results of a clinical study on tolerance where infants
were fed one of four different formulas. Three different formulas of the invention
and a control formula (identical but lacking the xanthan gum tolerance improver) were
utilized. The masked, randomized, parallel tolerance study was conducted on healthy,
term infants, 28 days or less in age. The infants were fed commercially-labeled Alimentum_
Protein Hydrolysate Formula With Iron (Ross Products Division, Abbott Laboratories)
in a ready-to-feed composition, for one week as a baseline. Immediately thereafter,
they randomly received either a control formula or one of formulas B, C or D. The
composition of the control formula was identical to that of formulas B-D, except for
the presence of differing amounts of xanthan gum in the formulas B-D. The composition
of all four formulas is provided in Tables II and II A. The control and formulas B-D
were provided in powdered form in metal cans of sufficient size to contain 350 grams
when reconstituted with water.
[0033] Infants were eligible for the study if they were judged to be in good health; were
full-term with a gestational age of 37 to 42 weeks; had a birth weight greater than
2500 g; were at least 28 days of age; were exclusively formula fed at the time of
the study; had parents who voluntarily signed an informed consent form; had parents
who agreed not to administer mineral or vitamin supplements; had parents who agreed
to feed their infant only the study formula for the duration of the study; were the
product of a single birth pregnancy; did not have a maternal medical history which
may have adversely affected the fetus such as diabetes, tuberculosis, perinatal infections,
or substance abuse; did not show evidence of cardiac, respiratory, gastrointestinal,
hematological, or metabolic disease; and did not have a birth weight greater than
the 95th percentile (NCHS (National Center for Health Statistics)) for infants whose
mothers had gestational diabetes.
[0034] Infants were identified by the investigators from the local population, and eligible
infants were recruited. A total of 182 infants, from three different sites, were enrolled
in the study. Of the initial 182, 45 exited during the baseline period and never received
the control or formulas B-D. Of the 137 who received either the control or one of
the formulas B-D, 12 infants failed to complete the study.
[0035] Day one of the study was defined as the day of enrollment into the study. On day
one, demographic/entrance data was collected and infants were weighed unclothed. Parents
received approximately twelve 32-fl oz cans of the baseline Alimentum Protein Hydrolysate
Formula With Iron in a ready to feed composition. Parents were instructed to continue
feeding their current formula until 6:00 p.m. on day one, and then to begin feeding
the baseline formula on the first feed after 6:00 p.m on day one. Intake and stool
data were collected beginning on day one at 6:00 p.m. and ending at 5:59 p.m. on day
seven. Parents also recorded the characteristics of their infants stools, volume of
formula consumed at each feeding and incidence of spit up and vomiting.
[0036] On day eight of the study, records completed by parents were reviewed by study personnel
for completeness and accuracy, infants were reweighed and questionnaires regarding
formula satisfaction and feeding and stool patterns were completed by the parents.
Parents returned unused baseline formula and were given approximately four cans of
one of the assigned formulas the control, B, C or D. Parents were instructed to continue
feeding the baseline formula until 6:00 p.m. on day eight, and to begin feeding the
assigned formula thereafter and record feeding and stool information. Intake and stool
data were collected from day eight starting at 6:00 p.m. and ending at 5:59 p.m. on
study day fourteen. Six days of data were collected on the control and formulas B-D.
As with the baseline feedings, the dietary intake and stool records completed by parents
during days eight to fourteen were reviewed by study personnel at a visit on day fifteen.
On day fifteen, infants were weighed, questionnaires were completed and parents returned
any unused portions of the formulas.
Statistical Analysis
[0037] Primary variables were average daily stool number, mean rank stool consistency and
incidence of vomiting and spit up. The primary analysis consisted of an analysis of
the primary outcome variables on an intent-to-treat basis. The secondary analysis
was conducted with study completers. The study period data were analyzed using one-way
analysis of variance with site as blocking factor. Additionally, an analysis of covariance
with study period data as response, and baseline data as covariate was done as a confirmatory
analysis. Transformations (ranking arcsine of the square root) were applied when appropriate.
Categorical/ordinal data were analyzed using contingency table methods. All tests
were two-sided and performed at the 0.05 significance level. The significance level
in the three primary analysis was adjusted for multiplicity of testing using Holm's
stepdown Bonferroni method.
Results
[0038] No statistically significant differences were observed in ethnicity or age on study
day one. Significant differences were observed in gender distribution among groups
at entry. (P <0.05). Weight at day one was significantly greater in the group fed
formula B, compared to the group fed the control formula on day one. Significantly
more infants fed the control formula exited due to intolerance than compared to those
receiving formulas B, C or D (those containing the xanthan gum tolerance improver).
[0039] Statistically significant differences were observed among groups in the average daily
number of stools (P=0.003 adjusted for multiplicity). Infants fed the control formula
passed significantly more stools than compared to infants fed formulas B (P=0.0001)
and D (P=0.0073). Infants fed the control formula passed a mean of 2.7± 0.2 stools
per day and infants fed formula B and D passed a mean of 1.6 ± 0.2 and 2.1 ± 0.3 stools
per day during the experimental period (days 8-14). There were no statistically significant
differences among groups in mean rank stool consistency. The percent of stools which
were watery were significantly different among groups. Infants fed the control formula
had significantly more stools which were watery compared to the formula C and D groups
(P<0.01) when baseline measurements were added as covariate in the analysis. No other
significant differences were observed among groups for other stool parameters (loose/mushy,
soft, formed). Results on daily number of stools, mean rank stool consistency, watery,
loose/mushy stools, soft stools and formed stools are reported in Table III.
[0040] No statistically significant differences were observed among groups in the percent
of feedings with spit up or the percent of feedings with vomiting. No statistically
significant differences were observed in the number of feedings per day, intakes in
ml per day, or intakes in ml per kg per day among groups. Results on spit ups, vomiting,
feedings per day, intakes in ml per day and intakes in ml per kg per day are reported
in Table IV.
[0041] No significant differences were observed among groups in weight NCHS Z-scores at
day fifteen, or weight gain during the experimental period (days 8-14). A significant
difference was observed among groups in weight of infants at the day 15 visit. Infants
fed formula B were significantly heavier than infants fed the control formula (P<0.01)
as they had been at day one. When day eight weight was used as a covariate, no significant
differences were observed among groups in the weight at the end of the study. Results
are reported in Table V.
Discussion
[0042] The results of the study confirmed that the addition of xanthan gum to a formula
improved the tolerance of infants fed such a formula. Infants fed formulas B, C and
D (with xanthan gum tolerance improver) generally passed fewer stools per day than
those fed the control formula (Table II). Corroborative results found that infants
fed formulas B, C and D were judged by parents to have fewer days with too many stools
compared to those fed the control formula. In addition, the number of infants exiting
due to formula intolerance was significantly lower in the groups fed formulas B, C
and D compared to the group fed the control formula. Results are shown in Table VI.
The percentage of exits for the group fed the control formula, with no tolerance improver,
was 22%. Thus, the reduction in exits (0-6%) for infants fed formulas B, C and D were
clinically striking compared to the control. While the infants enrolled in this study
were healthy infants (with no known allergy or sensitivity to intact proteins), the
improved tolerance results achieved here should also be experienced by infants with
allergies or sensitivities to intact proteins who exhibit symptoms of intolerance
while on current hydrolysate formulas and by children over one who exhibit symptoms
of intolerance.
Example 2
[0043] A powdered formula is prepared by solubilizing approximately 3116 kg (6870 Ib.) corn
maltodextrin, 1404 kg (3095 Ib.) sucrose, 24.4 kg magnesium chloride, 54.9 kg potassium
citrate, 17.8 kg sodium chloride, 114.5 kg calcium phosphate, tribasic, 25.5 kg calcium
carbonate, 16.4 kg potassium chloride and 13.7 g potassium iodide in water al 71°C
(160°F) to make an aqueous solution. The amount of water used in making the aqueous
solution will be optimized for the particular manufacturing equipment utilized. This
solution is blended with a second solution containing 867 kg (1911 Ib.) MCT oil, 130.6
kg diacetyl tartaric acid esters of mono- and diglycerides, 26.1 kg mono- and diglycerides,
916 kg (2020 Ib.) high oleic safflower oil, 0.50 kg (1.1 Ib.) mixed tocopherols, 732
kg (1613 Ib.) soy oil, 2.1 kg ascorbyl palmitate and 3.2 kg of a vitamin premix containing
vitamin A palmitate, vitamin E acetate, phylloquinone and vitamin D3 to form a slurry.
This slurry is mixed for a minimum of 30 minutes up to two hours at a temperature
of 68 to 74°C. This slurry is emulsified at 1000 psi, homogenized through a two-stage
homogenizer at 2500 psi/500 psi and cooled through a plate heat exchanger to approximately
4°C. Solutions containing free amino acids, water soluble vitamins and trace minerals
are added to the processed slurry. The slurry is heated to 74.4 to 85°C for a minimum
of 16 seconds and spray dried to obtain a powder having a moisture content of approximately
1.5%. The spray dried powder is dry blended with approximately 1676 kg (3430 lb.)
casein hydrolysate and 51.2 kg of xanthatn gum.
Example 3
[0044] A powdered formula is prepared by solubilizing approximately 3116 kg (6870 Ib.) corn
maltodextrin, 1404 kg (3095 Ib.) sucrose, 24.4 kg magnesium chloride, 54.9 kg potassium
citrate, 17.8 kg sodium chloride, 114.5 kg calcium phosphate, tribasic, 25.5 kg calcium
carbonate, 16.4 kg potassium chloride and 13.7 g potassium iodide in water at 71 °C
(160°F) to make an aqueous solution. The amount of water used in making the aqueous
solution will be optimized for the particular manufacturing equipment utilized. This
solution is blended with a second solution containing 867 kg (1911 Ib.) MCT oil, 130.6
kg diacetyl tartaric acid esters of mono- and diglycerides, 26.1 kg mono- and diglycerides,
916 kg (2020 lb.) high oleic safflower oil, 0.50 kg (1.1 lb.) mixed tocopherols, 732
kg (1613 lb.) soy oil, 2.1 kg ascorbyl palmitate and 3.2 kg of a vitamin premix containing
vitamin A palmitate, vitamin E acetate, phylloquinone and vitamin D3 to form a slurry.
This slurry is mixed for a minimum of 30 minutes up to two hours at a temperature
of 68 to 74°C. This slurry is emulsified at 1000 psi, homogenized through a two-stage
homogenizer at 2500 psi/500 psi and cooled through a plate heat exchanger to approximately
4°C. Approximately 1676 kg (3430 Ib.) casein hydrolysate is blended in water for a
minimum of 30 minutes up to two hours at a temperature of 68-74°C. This slurry is
emulsified at 1000 psi, homogenized through a two-stage homogenizer at 2500 psi/500
psi, cooled through a plate heat exchanger to approximately 4°C and added to the carbohydrate/fat/lipid
blend. Solutions containing free amino acids, water soluble vitamins and trace minerals
are added to the processed slurry. The slurry is heated to 74.4 to 85°C for a minimum
of 16 seconds and spray dried to obtain a powder having a moisture content of approximately
1.5%. The spray dried powder is dry blended with 51.2 kg of xanthan gum.
Example 4
[0045] A powdered formula is prepared by solubilizing approximately 3116 kg (6870 Ib.) corn
maltodextrin, 1404 kg (3095 Ib.) sucrose, 24.4 kg magnesium chloride, 54.9 kg potassium
citrate, 17.8 kg sodium chloride, 114.5 kg calcium phosphate, tribasic, 25.5 kg calcium
carbonate, 16.4 kg potassium chloride and 13.7 g potassium iodide in water at 71 °C
(160°F) to make an aqueous solution. The amount of water used in making the aqueous
solution will be optimized for the particular manufacturing equipment utilized. This
solution is blended with a second solution containing 867 kg (1911 Ib.) MCT oil, 130.6
kg diacetyl tartaric acid esters of mono and diglycerides, 26.1 kg mono- and diglycerides,
916 kg (2020 Ib.) high oleic safflower oil, 0.50 kg (1.1 Ib.) mixed tocopherols, 732
kg (1613 Ib.) soy oil, 2.1 kg ascorbyl palmitate, 3.2 kg of a vitamin premix containing
vitamin A palmitate, vitamin E acetate, phylloquinone and vitamin D3 and the xanthan
gum to form a slurry. This slurry is mixed for a minimum of 30 minutes up to two hours
at a temperature of 68 to 74°C. This slurry is emulsified at 1000 psi, homogenized
through a two-stage homogenizer at 2500 psi/500 psi and cooled through a plate heat
exchanger to approximately 4°C. Approximately 1676 kg (3430 Ib.) casein hydrolysate
is blended in water for a minimum of 30 minutes up to two hours at a temperature of
68-74°C. This slurry is emulsified at 1000 psi, homogenized through a two-stage homogenizer
at 2500 psi/500 psi, cooled through a plate heat exchanger to approximately 4°C and
added to the carbohydrate/fat/lipid blend. Solutions containing free amino acids,
water soluble vitamins and trace minerals are added to the processed slurry. The slurry
is heated to 74.4 to 85°C for a minimum of 16 seconds and spray dried to obtain a
powder having a moisture content of approximately 1.5%.
Example 5
[0046] A powdered formula is prepared by solubilizing approximately 3116 kg (6870 Ib.) rice
maltodextrin, 1404 kg (3095 lb.) sucrose, 24.4 kg magnesium chloride, 54.9 kg potassium
citrate, 17.8 kg sodium chloride, 114.5 kg calcium phosphate, tribasic, 25.5 kg calcium
carbonate, 16.4 kg potassium chloride and 13.7 g potassium iodide in water at 71°C
(160°F) to make an aqueous solution. This solution is blended with a second solution
containing 867 kg (1911 lb.) MCT oil, 130.6 kg diacetyl tartaric acid esters of mono-
and diglycerides, 26.1 kg mono- and diglycerides, 916 kg (2020 lb.) high oleic safflower
oil, 0.50 kg (1.1 lb.) mixed tocopherols, 732 kg (1613 lb.) soy oil, 2.1 kg ascorbyl
palmitate and 3.2 kg of a vitamin premix containing vitamin A palmitate, vitamin E
acetate, phylloquinone and vitamin D3. to form a slurry. This slurry is mixed for
a minimum of 30 minutes up to two hours at a temperature of 68 to 74°C. This slurry
is emulsified at 1000 psi, homogenized through a two stage homogenizer at 2500 psi/500
psi and cooled through a plate heat exchanger to approximately 4°C. Solutions containing
water soluble vitamins and trace minerals are added to the processed slurry. The slurry
is heated to 74.4 to 85°C for a minimum of 16 seconds and spray dried to obtain a
powder having a moisture content of approximately 1.5%. The spray dried powder is
dry blended with approximately 1676 kg (3430 lb.) whey protein hydrolysate, free amino
acids, 41.2 kg locust bean gum and 51.2 kg of xanthan gum.
TABLE I RANGES OF CARBOHYDRATE, LIPID AND PROTEIN PER 100 KCAL, PER 100 GRAMS POWDER
AND PER LITER (AS FED CONCENTRATION)
Nutrient (g) |
Range |
Per 100 kcal |
Per 100 grams powder |
Per liter (as fed concentration) |
Carbohydrate |
Broadest |
8-16 |
30-90 |
53-107 |
|
Preferred |
9.4-12.3 |
48-59 |
64-83 |
Lipid |
Broadest |
3-6 |
15-30 |
22-40 |
|
Preferred |
4.7-5.6 |
22-28 |
32-38 |
Protein |
Broadest |
1.8-3.3 |
8-17 |
12-22 |
|
Preferred |
2.4-3.3 |
11-17 |
16-22 |
TABLE II NUTRIENT CONTENT OF CONTROL AND FORMULAS B, C, AND D*
Nutrient1 |
Per Liter |
Per 100 kcal |
Per 100 g Powder |
Protein (g) |
18.6 |
2.75 |
13.9 |
Fat (g) |
37.5 |
5.55 |
28.1 |
Carbohydrate (g) |
73 |
10.8 |
54.6 |
Calcium (mg) |
710 |
105 |
531 |
Phosphorus (mg) |
507 |
75 |
379 |
Magnesium (mg) |
51 |
7.5 |
38.1 |
lron (mg) |
12.2 |
1.8 |
9.1 |
Zinc (mg) |
5 |
0.74 |
3.7 |
Manganese (mcg) |
34 |
5 |
25 |
Copper (mcg) |
500 |
74 |
374 |
lodine (mcg) |
100 |
14.8 |
75 |
Sodium (mg) |
297 |
43.9 |
222 |
Potassium (mg) |
800 |
118.3 |
598 |
Chloride (mg) |
541 |
80 |
405 |
Selenium (mcg) |
16 |
2.4 |
12 |
Vitamin A (IU) |
2,200 |
325 |
1,646 |
Vitamin D (IU) |
400 |
59 |
299 |
Vitamin E (IU) |
20.8 |
3.1 |
15.6 |
Vitamin K1 (IU) |
101 |
14.9 |
75.5 |
Thiamin (mcg) |
580 |
86 |
434 |
Riboflavin (mcg) |
600 |
89 |
449 |
Vitamin B-6 (mcg) |
530 |
78 |
396 |
Vitamin B-12 (mcg) |
3 |
0.44 |
2.24 |
Niacin (mg) |
9 |
1.33 |
6.73 |
Folic Acid (mcg) |
100 |
14.8 |
74.8 |
Panthothenic Acid (mg) |
5 |
0.74 |
3.74 |
Biotin (mcg) |
30 |
4.4 |
22.4 |
Vitamin C (mg) |
90 |
13.3 |
67.3 |
Choline (mg) |
53 |
7.8 |
39.6 |
Inositol (mg) |
30 |
4.4 |
22.4 |
* Values are minimum except for carbohydrate which is maximum based on minimum protein
and fat. |
[0047] Control formula ingredients: corn maltodextrin, casein hydrolysate (enzymatically
hydrolyzed and charcoal treated), sucrose, high oleic safflower oil, fractionated
coconut oil (medium-chain triglycerides), soy oil, diacetyl tartaric acid esters of
mono- and diglycerides, calcium phosphate tribasic, potassium citrate, mono- and diglycerides,
calcium carbonate, magnesium chloride, ascrobic acid, L-cystine dihydrochloride, sodium
chloride, potassium chloride, L-tyrosine, choline chloride, L-tryptophan, ferrous
sulfate, taurine, m-inositol, ascorbyl palmitate, vitamin E acetate, zinc sulfate,
mixed tocopherols, L-carnitine, niacinamide, calcium pantothenate, cupric sulfate,
vitamin A palmitate, thiamine chloride hydrochloride, riboflavin, pyridoxine hydrochloride,
folic acid, potassium iodide, manganese sulfate, phylloquinone, biotin, sodium selenite,
vitamin D
3, cyanocobalamin.
[0048] Formulas B, C and D Ingredients: corn maltodextrin, casein hydrolysate (enzymatically
hydrolyzed and charcoal treated), sucrose, high oleic safflower oil, fractionated
coconut oil (medium-chain triglycerides), soy oil, diacetyl tartaric acid esters of
mono- and diglycerides, calcium phosphate tribasic, potassium citrate, xanthan gum,
mono and diglycerides, calcium carbonate, magnesium chloride, ascrobic acid, L-cystine
dihydrochloride, sodium chloride, potassium chloride, L-tyrosine, choline chloride,
L-tryptophan, ferrous sulfate, taurine, m-inositol, ascorbyl palmitate, vitamin E
acetate, zinc sulfate, mixed tocopherols, L-camitine, niacinamide, calcium pantothenate,
cupric sulfate, vitamin A palmitate, thiamine chloride hydrochloride, riboflavin,
pyridoxine hydrochloride, folic acid, potassium iodide, manganese sulfate, phylloquinone,
biotin, sodium selenite, vitamin D
3, cyanocobalamin.
TABLE II A AMOUNT OF XANTHAN GUM (MG) IN CONTROL AND FORMULAS B, C, AND D
Formula |
Per Liter |
Per 100 kcal |
Per 100 g Powder |
A |
0 |
0 |
0 |
B |
500 |
74 |
374 |
C |
1,000 |
148 |
748 |
D |
1,500 |
222 |
1,122 |
TABLE III Number Of Stools Per Day, Mean Rank Stool Consistency, And Percent Of Watery,
Loose/Mushy, Soft And Formed Stools During Baseline and Experimental Periods1
Parameter |
Group/Formula |
Baseline (Days 1-7) |
Experimental (Days 1-8) |
Stools (number/day) |
Control |
2.7 ± 0.2 |
2.7 ± 0.2 |
|
B |
2.6 ± 0.3 |
1.6 ± 0.2 |
|
C |
2.6 ± 0.3 |
1.9 ± 0.2 |
|
D |
2.5 ± 0.3 |
2.1 ± 0.3 |
Mean Rank Stool Consistency2 |
Control |
2.5 ± 0.1 |
2.1 ± 0.1 |
|
B |
2.4 ± 0.1 |
2.0 ± 0.1 |
|
C |
2.3 ±0.1 |
2.3 ±0.1 |
|
D |
2.3 ±0.1 |
2.3 ±0.1 |
% Watery Stools |
Control |
6.9 ± 2.3 |
29.0 ± 6.1 |
|
B |
8.9 ± 2.7 |
22.6 ± 5.4 |
|
C |
13.2 ± 3.6 |
11.0 ± 4.3 |
|
D |
11.6 ± 2.7 |
14.2 ± 4.2 |
% Loose/Mushy Stools |
Control |
41.6 ± 5.1 |
42.1 ± 5.5 |
|
B |
47.7 ± 5.3 |
51.9 ± 6.3 |
|
C |
49.1 ± 5.4 |
51.3 ± 7.2 |
|
D |
52.6 ± 4.3 |
42.6 ± 6.2 |
% Soft Stools |
Control |
45.4 ± 5.4 |
22.6 ± 4.9 |
|
B |
38.0 ± 5.4 |
25.4 ± 6.3 |
|
C |
31.6 ± 5.0 |
33.8 ± 7.5 |
|
D |
31.8 ± 4.0 |
37.0 ± 5.8 |
% Formed Stools |
Control |
5.7 ± 1.9 |
6.3 ± 3.2 |
|
B |
5.3 ± 1.9 |
0.0 ± 0.0 |
|
C |
5.8 ± 2.7 |
2.2 ± 1.4 |
|
D |
3.4 ± 1.2 |
5.4 ± 2.3 |
1 Mean ± standard error of the mean. |
2 1 = watery, 2 = loose/mushy, 3 = soft, 4 = formed, 5 = hard. |
TABLE IV Number Of Feedings Per Day, Average Intake, and Percent of Feeding With Spit
Up, Vomiting And Spit Up And Vomiting During Baseline And Experimental Periods1
Parameter |
Group/Formula |
Baseline (Days 1-7) |
Experimental (Days 1-8) |
Number of feedings/day |
Control |
7.5 ± 0.2 |
7.3 ± 0.3 |
|
B |
7.4 ±0.2 |
7.3 ± 0.3 |
|
C |
7.4 ± 0.3 |
7.1 ± 0.3 |
|
D |
7.2 ± 0.2 |
6.9 ± 0.2 |
Average intake (ml/day) |
Control |
524 ±19 |
568 ± 26 |
|
B |
556 ± 28 |
624 ± 32 |
|
C |
525 ± 21 |
605 ± 24 |
|
D |
551 ± 26 |
608 ± 21 |
% Feedings with Spit Up |
Control |
11.1 ± 2.0 |
13.3 ± 3.5 |
|
B |
17.0 ± 3.1 |
11.7 ± 2.1 |
|
C |
23.8 ± 4.3 |
15.0 ± 4.2 |
|
D |
11.5 ± 2.2 |
9.0 ± 1.8 |
% of Subjects with any Vomiting |
Control |
8.2 ± 2.9 |
2.0 ± 1.0 |
|
B |
4.1 ± 1.4 |
3.9 ± 2.9 |
|
C |
7.3 ± 2.6 |
3.6 ± 2.0 |
|
D |
4.8 ± 1.6 |
2.6 ± 1.0 |
% of Feedings with Spit Up or Vomit |
Control |
19.3 ± 3.5 |
15.3 ± 3.5 |
|
B |
21.0 ± 3.8 |
15.6 ± 3.3 |
|
C |
31.2 ± 5.1 |
18.6 ± 4.5 |
|
D |
16.3 ± 3.2 |
11.5 ± 2.3 |
1 Mean ± standard error of the mean. |
TABLE V Weight Gain Of Infants During The Baseline And Experimental Periods1
Parameter |
Group/Formula |
Baseline (Days 1-7) |
Experimental (Days 8-14) |
Weight Gain (grams/day) |
Control2 |
30.2 ± 2.7 |
31.1 ± 2.9 |
|
B3 |
33.6 ± 2.6 |
34.4 ± 2. 1 |
|
C4 |
29.3 ± 2.8 |
30.9 ± 2.8 |
|
D5 |
26.6 ± 2.4 |
34.1 ± 2.7 |
1 Mean ± standard error of the mean. |
2 Number of infants: 44 baseline, 35 experimental. |
3 Number of infants: 43 baseline, 35 experimental. |
4 Number of infants: 39 baseline, 28 experimental. |
5 Number of infants: 44 baseline, 36 experimental. |
TABLE VI Subject Outcome By Feeding (n=182)
Exit Status |
Formula |
|
Control |
B |
C |
D |
Successful Completion |
29 |
33 |
28 |
35 |
Early Exit (Days 8-14)1 |
8 |
2 |
0 |
2 |
Baseline Exit (Days 1-7) |
9 |
11 |
17 |
8 |
Percentage of Exits2 |
22 |
6 |
0 |
5 |
Total |
46 |
46 |
45 |
45 |
1 All due to formula intolerance or parental dissatisfaction except for one infant
in the 1500 group. |
2 Percent = [early exits (days 8-14) / [successful completers + baseline exits (days
1-7)]] x 100 |
1. A pediatric formula comprising per liter from 53 to 107 grams carbohydrate, 22 to
40 grams lipid, 12 to 22 grams protein, and a tolerance improver comprising 250 to
2500 milligrams xanthan gum.
2. A pediatric formula as defined in claim 1 wherein the xanthan gum comprises from 500
to 1500 milligrams.
3. A pediatric formula as defined in claim 1 wherein the xanthan gum comprises from 750
to 1000 milligrams.
4. A pediatric formula as defined in claim 1 wherein the carbohydrate comprises from
64 to 83 grams.
5. A pediatric formula as defined in claim 1 wherein the lipid comprises from 32 to 38
grams.
6. A pediatric formula as defined in claim 1 wherein the protein comprises from 16 to
22 grams.
7. A pediatric formula in a powdered form which comprises, based on 100 grams of powder,
30 to 90 grams carbohydrate, 15 to 30 grams lipid, 8 to 17 grams protein, and 188
to 1880 milligrams xanthan gum.
8. A pediatric formula as defined in claim 7 wherein the xanthan gum comprises from 375
to 1125 milligrams.
9. A pediatric formula as defined in claim 7 wherein the xanthan gum comprises from 565
to 750 milligrams.
10. A pediatric formula as defined in claim 7 wherein the carbohydrate comprises from
48 to 59 grams.
11. A pediatric formula as defined in claim 7 wherein the lipid comprises from 22 to 28
grams.
12. A pediatric formula as defined in claim 7 wherein the protein comprises from 11 to
17 grams.
13. A pediatric formula as defined in any of claims 1-12 further comprising vitamins and
minerals.
14. A pediatric formula as defined in any of claims 1-12 wherein the vitamins and minerals
are selected from the group consisting of calcium, phosphorus, sodium, chloride, magnesium,
manganese, iron, copper, zinc, selenium, iodine, Vitamins A, E, C, D, K and the B
complex, and mixtures thereof.
15. A pediatric formula as defined in any of claims 1-12 wherein the lipid is selected
from the group consisting of coconut oil, soy oil, corn oil, olive oil, safflower
oil, high oleic safflower oil, MCT oil (medium chain triglycerides), sunflower oil,
high oleic sunflower oil, palm oil, palm olein, canola oil, lipid sources of arachidonic
acid and docosahexaneoic acid, and mixtures thereof.
16. A pediatric formula as defined in any of claims 1-12 wherein the protein comprises
intact protein selected from the group consisting of soy based protein, milk based
protein, casein protein, whey protein, rice protein, beef collagen, pea protein, potato
protein, and mixtures thereof.
17. A pediatric formula as defined in any of daims 1-12 wherein the protein comprises
hydrolyzed protein selected from the group consisting of soy protein hydrolysate,
casein protein hydrolysate, whey protein hydrolysate, rice protein hydrolysate, potato
protein hydrolysate, fish protein hydrolysate, egg albumen hydrolysate, gelatin protein
hydrolysate, a combination of animal and vegetable protein hydrolysates, and mixtures
thereof.
18. A pediatric formula as defined in any of claims 1-12 wherein the protein comprises
free amino acids selected from the group consisting of tryptophan, tyrosine, cystine,
taurine, L-methionine, L-arginine, and camitine, and mixtures thereof.
19. A pediatric formula as defined in any of claims 1-12 wherein the carbohydrate is selected
from the group consisting of hydrolyzed, intact, natural and chemically modified starches
sourced from com, tapioca, rice or potato in waxy or non waxy forms; sugars such as
glucose, fructose, lactose, sucrose, maltose, high fructose corn syrup; and mixtures
thereof.
20. A pediatric formula as defined in any of claims 1-12 further comprising a stabilizer,
selected from the group consisting of gum arabic, gum ghatti, gum karaya, gum tragacanth,
agar, furcellaran, guar gum, gellan gum, locust bean gum, pectin, low methoxyl pectin,
gelatin, microcrystalline cellulose, CMC, methylcellulose hydroxypropyl methyl cellulose,
hydroxypropyl cellulose, dextran, carrageenans, and mixtures thereof.
21. Use of a formula according to any of claims 1-20 in the manufacture of a formula for
providing nutrition to a pediatric patient.
22. Use of a formula according to any of claims 1-20 in the manufacture of a formula for
improving tolerance in a pediatric patient
1. Eine pädiatrische Formulierung, die pro Liter von 53 bis 107 Gramm Kohlenhydrat, 22
bis 40 Gramm Lipid, 12 bis 22 Gramm Protein und einen Toleranzverbesserer umfaßt,
der 250 bis 2500 Milligramm Xanthangummi umfaßt.
2. Eine pädiatrische Formulierung, wie in Anspruch 1 definiert, worin das Xanthangummi
von 500 bis 1500 Milligramm umfaßt.
3. Eine pädiatrische Formulierung, wie in Anspruch 1 definiert, worin das Xanthangummi
von 750 bis 1000 Milligramm umfaßt.
4. Eine pädiatrische Formulierung, wie in Anspruch 1 definiert, worin das Kohlenhydrat
von 64 bis 83 Gramm umfaßt.
5. Eine pädiatrische Formulierung, wie in Anspruch 1 definiert, worin das Lipid von 32
bis 38 Gramm umfaßt.
6. Eine pädiatrische Formulierung, wie in Anspruch 1 definiert, worin das Protein von
16 bis 22 Gramm umfaßt.
7. Eine pädiatrische Formulierung in einer pulverisierten Form, welche, basierend auf
100 Gramm des Pulvers, 30 bis 90 Gramm Kohlenhydrat, 15 bis 30 Gramm Lipid, 8 bis
17 Gramm Protein und 188 bis 1880 Milligramm Xanthangummi umfaßt.
8. Eine pädiatrische Formulierung, wie in Anspruch 7 definiert, worin das Xanthangummi
von 375 bis 1125 Milligramm umfaßt.
9. Eine pädiatrische Formulierung, wie in Anspruch 7 definiert, worin das Xanthangummi
von 565 bis 750 Milligramm umfaßt.
10. Eine pädiatrische Formulierung, wie in Anspruch 7 definiert, worin das Kohlenhydrat
von 48 bis 59 Gramm umfaßt.
11. Eine pädiatrische Formulierung, wie in Anspruch 7 definiert, worin das Lipid von 22
bis 28 Gramm umfaßt.
12. Eine pädiatrische Formulierung, wie in Anspruch 7 definiert, worin das Protein von
11 bis 17 Gramm umfaßt.
13. Eine pädiatrische Formulierung, wie in irgendeinem der Ansprüche 1 bis 12 definiert,
die weiter Vitamine und Mineralien umfaßt.
14. Eine pädiatrische Formulierung, wie in irgendeinem der Ansprüche 1 bis 12 definiert,
worin die Vitamine und Mineralien gewählt sind aus der Gruppe bestehend aus Kalzium,
Phosphor, Natrium, Chlorid, Magnesium, Mangan, Eisen, Kupfer, Zink, Selen, Jod, den
Vitaminen A, E, C, D, K und dem B Komplex und Mischungen davon.
15. Eine pädiatrische Formulierung, wie in irgendeinem der Ansprüche 1 bis 12 definiert,
worin das Lipid gewählt ist aus der Gruppe bestehend aus Kokosnußöl, Sojaöl, Maiskeimöl,
Olivenöl, Saffloröl, Saffloröl mit hohem Ölsäuregehalt, MCT Öl (mittelkettige Triglyceride),
Sonnenblumenöl, Sonnenblumenöl mit hohem Ölsäuregehalt, Palmöl, Palmolein, Canolaöl,
Lipidquellen von Arachidonsäure und Docosahexaensäure, und Mischungen davon.
16. Eine pädiatrische Formulierung, wie in irgendeinem der Ansprüche 1 bis 12 definiert,
worin das Protein intaktes Protein umfaßt, gewählt aus der Gruppe bestehend aus Soja-basiertem
Protein, Milch-basiertem Protein, Caseinprotein, Molkeprotein, Reisprotein, Fleischkollagen,
Erbsenprotein, Kartoffelprotein und Mischungen davon.
17. Eine pädiatrische Formulierung, wie in irgendeinem der Ansprüche 1 bis 12 definiert,
worin das Protein hydrolysiertes Protein umfaßt, gewählt aus der Gruppe bestehend
aus Sojaproteinhydrolysat, Caseinproteinhydrolysat, Molkenproteinhydrolysat, Reisproteinhydrolysat,
Kartoffelproteinhydrolysat, Fischproteinhydrolysat, Eiweißhydrolysat, Gelatineproteinhydrolysat,
einer Kombination aus tierischen und pflanzlichen Proteinhydrolysaten und Mischungen
davon.
18. Eine pädiatrische Formulierung, wie in irgendeinem der Ansprüche 1 bis 12 definiert,
worin das Protein freie Aminosäuren umfaßt, gewählt aus der Gruppe bestehend aus Tryptophan,
Tyrosin, Cystin, Taurin, L-Methionin, L-Arginin und Carnitin und Mischungen davon.
19. Eine pädiatrische Formulierung, wie in irgendeinem der Ansprüche 1 bis 12 definiert,
worin das Kohlenhydrat gewählt ist aus der Gruppe bestehend aus hydrolysierten, intakten,
natürlichen und chemisch modifizierten Stärken, abgeleitet von Weizen, Tapioka, Reis
oder Kartoffeln in wachsähnlichen oder nicht wachsähnlichen Formen; Zuckern, wie zum
Beispiel Glukose, Fruktose, Laktose, Saccharose, Maltose, Maisstärkesirup mit hohem
Fruktosegehalt; und Mischungen davon.
20. Eine pädiatrische Formulierung, wie in irgendeinem der Ansprüche 1 bis 12 definiert,
die weiterhin einen Stabilisator umfaßt, gewählt aus der Gruppe bestehend aus Gummi
arabicum, Gummi Ghatti, Karayagummi, Tragantgummi, Agar, Furcellaran, Guargummi, Gellangummi,
Johannisbrotgummi, Pectin, Niedermethoxylpectin, Gelatine, mikrokristalline Zellulose,
CMC, Methylzellulose, Hydroxypropylmethylzellulose, Hydroxypropylzellulose, Dextran,
Carrageenan und Mischungen davon.
21. Verwendung einer Formulierung gemäß irgendeinem der Ansprüche 1 bis 20 in der Herstellung
einer Formulierung zur Bereitstellung von Nahrung an einen pädiatrischen Patienten.
22. Verwendung einer Formulierung gemäß irgendeinem der Ansprüche 1 bis 20 in der Herstellung
einer Formulierung zur Verbesserung der Toleranz in einem pädiatrischen Patienten.
1. Formule pédiatrique comprenant par litre de 53 à 107 grammes de glucides, 22 à 40
grammes de lipides, 12 à 22 grammes de protéines, et un améliorant de la tolérance
comprenant 250 à 2 500 milligrammes de gomme xanthique.
2. Formule pédiatrique selon la revendication 1, dans laquelle la gomme xanthique constitue
de 500 à 1 500 milligrammes.
3. Formule pédiatrique selon la revendication 1, dans laquelle la gomme xanthique constitue
de 750 à 1 000 milligrammes.
4. Formule pédiatrique selon la revendication 1, dans laquelle les glucides constituent
de 64 à 83 grammes.
5. Formule pédiatrique selon la revendication 1, dans laquelle les lipides constituent
de 32 à 38 grammes.
6. Formule pédiatrique selon la revendication 1, dans laquelle les protéines constituent
de 16 à 22 grammes.
7. Formule pédiatrique sous forme pulvérulente qui comprend, sur la base de 100 grammes
de poudre, 30 à 90 grammes de glucides, 15 à 30 grammes de lipides, 8 à 17 grammes
de protéines et 188 à 1 880 milligrammes de gomme xanthique.
8. Formule pédiatrique selon la revendication 7, dans laquelle la gomme xanthique constitue
de 375 à 1 125 milligrammes.
9. Formule pédiatrique selon la revendication 7, dans laquelle la gomme xanthique constitue
de 565 à 750 milligrammes.
10. Formule pédiatrique selon la revendication 7, dans laquelle les glucides constituent
de 48 à 59 grammes.
11. Formule pédiatrique selon la revendication 7, dans laquelle les lipides constituent
de 22 à 28 grammes.
12. Formule pédiatrique selon la revendication 7, dans laquelle les protéines constituent
de 11 à 17 grammes.
13. Formule pédiatrique selon l'une quelconque des revendications 1 à 12, comprenant en
outre des vitamines et des minéraux.
14. Formule pédiatrique selon l'une quelconque des revendications 1 à 12, dans laquelle
les vitamines et minéraux sont choisis dans le groupe constitué de calcium, phosphore,
sodium, chlorure, magnésium, manganèse, fer, cuivre, zinc, sélénium, iode, vitamines
A, E, C, D, K et le complexe B, et des mélanges de ceux-ci.
15. Formule pédiatrique selon l'une quelconque des revendications 1 à 12, dans laquelle
les lipides sont choisis dans le groupe constitué d'huile de noix de coco, d'huile
de soja, d'huile de mais, d'huile d'olive, d'huile de carthame, d'huile de carthame
à forte teneur en acide oléique, d'huile à MCT (triglycérides à chaîne moyenne), d'huile
de tournesol, d'huile de tournesol à forte teneur en acide oléique, d'huile de palme,
d'oléine de palme, d'huile de colza, de sources lipidiques d'acide arachidonique et
d'acide docosahexanoïque et des mélanges de ceux-ci.
16. Formule pédiatrique selon l'une quelconque des revendications 1 à 12, dans laquelle
les protéines comprennent une protéine intacte choisie dans le groupe constitué d'une
protéine de soja, d'une protéine de lait, d'une protéine de caséine, d'une protéine
de blé, d'une protéine de riz, de collagène de boeuf, d'une protéine de pois, d'une
protéine de pomme de terre et des mélanges de ceux-ci.
17. Formule pédiatrique selon l'une quelconque des revendications 1 à 12, dans laquelle
les protéines comprennent une protéine hydrolysée choisie dans le groupe constitué
d'un hydrolysat de protéine de soja, d'un hydrolysat de protéine de caséine, d'un
hydrolysat de protéine de blé, d'un hydrolysat de protéine de riz, d'un hydrolysat
de protéine de pomme de terre, d'un hydrolysat de protéine de poisson, d'un hydrolysat
d'albumine d'oeuf, d'un hydrolysat de protéine de gélatine, d'une combinaison d'hydrolysat
de protéine animale et végétale et des mélanges de ceux-ci.
18. Formule pédiatrique selon l'une quelconque des revendications 1 à 12, dans laquelle
les protéines comprennent des acides aminés libres choisis dans le groupe constitué
du tryptophane, de la tyrosine, de la cystine, de la taurine, de la L-méthionine,
de la L-arginine et de la carnitine, et des mélanges de ceux-ci.
19. Formule pédiatrique selon l'une quelconque des revendications 1 à 12, dans laquelle
les glucides sont choisis dans le groupe constitué d'amidons modifiés chimiquement
et naturels intacts hydrolysés provenant de maïs, tapioca, riz ou pomme de terre sous
forme cireuse ou non cireuse ; sucres tels que le glucose, fructose, lactose, saccharose,
maltose, sirop de maïs à forte teneur en fructose et des mélanges de ceux-ci.
20. Formule pédiatrique selon l'une quelconque des revendications 1 à 12, comprenant en
outre un stabilisant, choisi dans le groupe constitué de la gomme arabique, de la
gomme ghatti, de la gomme de karaya, de la gomme adragante, de la gélose, de la furcellarane,
de la gomme guar, de la gomme gellane, de la gomme de caroube, de la pectine, de la
pectine à faible teneur en groupes méthoxyle, de la gélatine, de la cellulose microcristalline,
de la CMC, de la méthylcellulose, de l'hydroxypropylméthylcellulose, de l'hydroxypropylcellulose,
du dextran, de la carraghénine et des mélanges de ceux-ci.
21. Utilisation d'une formule selon l'une quelconque des revendications 1 à 20 dans 1a
fabrication d'une formule pour un apport nutritif à un patient pédiatrique.
22. Utilisation d'une formule selon l'une quelconque des revendications 1 à 20 dans la
fabrication d'une formule pour améliorer la tolérance chez un patient pédiatrique.